tbuckley/cabot-search huggingface dataset:
Abstract 15411: Life After the Valve, Analyzing Post-Procedural Anemia and Mortality in Transcatheter Aortic Valve Replacement Patients
Authors: David Polman, Siddharth Bhayani, Manoj Ambalavanan, Zaid Zayyad, Pranati Sreepathy, Carlos Dohse, Aamir Twing, David Tiu, Helena Dickens, Mayank M Kansal, Khalil Ibrahim, Adhir R Shroff
Journal: Circulation (2022)

Introduction: Transcatheter Aortic Valve Replacement (TAVR) has become the primary therapeutic option for many patients with severe aortic stenosis (AS). As a result, anemia is a prevalent co-morbidity amongst the TAVR population. Recent studies have demonstrated pre-procedural anemia is associated with increased long-term mortality in TAVR patients. However, the comparison of TAVR patients’ post-procedural anemia and its effect on mortality has not been fully investigated. Methods: Retrospective analysis of electronic medical records from 2018-2021 at the University of Illinois at Chicago and Jesse Brown VA Medical Center identified TAVR patients. Primary outcomes included all-cause mortality and significant bleeding at 6-months and 12-months post-TAVR. Results: We included 160 patients in the analysis. They were 122 males, 56.88% non-white, and an average age of 73.88. At 6-months, patients who experienced all-cause mortality had an average hemoglobin of 9.85 (g/dL) compared to an average hemoglobin of 11.31 in those patients that survived (p = 0.020). There was no significant difference in major bleeding events between the two groups (p = 0.974) as well as no significant difference in past-medical history, including hypertension, hyperlipidemia (HLD), diabetes mellitus, history of stroke and history of myocardial infarction. At 12-months, patients who experienced all-cause mortality had an average hemoglobin of 10.18 compared to an average hemoglobin of 11.36 in those patients that survived (p = 0.014). There was no significant difference in major bleeding events (p = 0.753) and no significant difference in past-medical history, except for hyperlipidemia. The prevalence of HLD was 59.09% in those that experienced all-cause mortality compared to 78.72% in those that did not (p = 0.045). Conclusions: Our results suggest that patients with lower hemoglobin levels after TAVR are at a greater risk of all-cause mortality compared to those with higher hemoglobin levels. These patients may benefit from closer follow-up after the procedure.
Abstract 15480: Liraglutide Inhibits Atherosclerotic Plaque Progression in Rabbits Through the Downregulation of Multiple Inflammatory and Metabolic Pathways
Authors: Mohamad B Kassab, Haitham Khraishah, Andrew Thrapp, Aatira Vijay, Du-Ri Song, Graham Spicer, Mazen Albaghdadi, Mohammed M Chowdhury, Paishiun Hsieh, Adam Mauskapf, Yoichiro Kawamura, Peter Libby, Peter Libby, Guillermo J Tearney, Farouc A Jaffer
Journal: Circulation (2022)

Background: Liraglutide, a GLP-1- receptor agonists approved for the treatment of type 2 diabetes and obesity confers a lower CVD mortality. However, mechanisms underlying this finding remain unknown, particularly in normoglycemic subjects. We investigated the effects of liraglutide on the progression and pathobiology of atherosclerosis using multimodal intravascular imaging in rabbits. Methods: Rabbits atherosclerosis (N=16) were induced by balloon injury of the abdominal aorta and cholesterol feeding for 6 weeks. Then, rabbits were imaged with intravascular ultrasound (IVUS) and near-infrared fluorescence optical coherence tomography (NIRF-OCT) for the analysis of plaque burden and plaque inflammation (ProSense VM110 NIRF agent, 4 mg/kg/iv) respectively. Next, rabbits were randomized into: Control (n=8) or liraglutide (n=8, 0.1 mg/kg/day) groups. Imaging was repeated after 4 weeks, followed by histopathology and RNA analysis. On per-slice basis (every 0.4 mm) of IVUS imaging, the percent atheroma volume (PAV) was measured across the 40 mm balloon injured area. Atheroma progression was quantified as the ΔPAV between 6 and 10 weeks. Results: IVUS analyses (3200 slices/16 rabbits) revealed that liraglutide significantly reduced plaque progression (ΔPAV, 1.5% [0.2-2.8] vs. 9.3% [6.7-13.0] control, p=0.05). In vivo distance-corrected VM110 cathepsin inflammatory plaque activity was similar (ΔNIRF average plaque 25.2 [-9.8- 62] vs. 22.6 [3.9- 52.5] nM control, p=0.72). Plaques from liraglutide-treated animals however exhibited fewer RAM11+ macrophages (21.3±11.4 vs. control 30.9±16.7 macrophages/section, p=0.01) stry. Both plaques showed similar αSMA (45.2±6.7% vs 52.4±1.2% αSMA+ area/section, p=0.327). Liraglutide decreased inflammatory RNA transcripts (IL-6 and TNF-α), and RNA-seq transcriptomic analysis revealed that liraglutide altered inflammatory and metabolic pathways (as CRP, CYP3A6, Apo-A4 and FMO3). Blood glucose was normal and similar between groups (p&gt;0.05). Conclusion: Liraglutide suppresses in vivo atherosclerotic plaque progression and plaque macrophage expression in normoglycemic rabbits. Further investigation of its plaque stabilizing effects in subjects with and without diabetes is warranted.
Abstract 15542: Immuno-Footprint of Myeloid Clusters in Human Abdominal Aortic Aneurysm
Authors: Michele Silvestro, Cristobal Rivera Martinez, John Vlahos, Muhammad Yogi Pratama, Puja Kumari, Rayan Sleiman Tellaoui, Thomas Maldonado, Bhama Ramkhelawon
Journal: Circulation (2022)

Inflammation is a hallmark of abdominal aortic aneurysms (AAA) with central roles ascribed to myeloid lineage effector cells. However, the dynamics of circulating immune subsets, their interaction, and direct roles in AAA are not completely understood. Here, in human AAA and control blood, we used unbiased Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITEseq) to investigate the complex spectrum of the proteome and transcriptome of the immune population, with refined characterization of immune subtypes in the peripheral blood. We also performed matched CITEseq for AAA tissues, allowing to define the fate and immuno-footprint of distinct immune clusters from blood to tissue. Fresh aortic specimens and blood from patients undergoing open AAA repair (n=5) and from healthy donors (n=2) were processed for CITEseq with a panel of antibodies encompassing 15 biologically relevant immune cell surface markers. After alignment, demultiplexing and cell cluster identification, analysis of proteo/transcriptome was performed in peripheral blood and in paired aneurysmal tissue datasets. Unsupervised clustering of CITEseq datasets from peripheral blood revealed eleven distinct clusters, with a unique signature of FCGR3A /CD16 + CD14 /CD14 lo monocytic populations in AAA patients, showing characteristics of myeloid-derived suppressor cells. Interestingly, we also unveiled that a subset of pro-inflammatory monocytes coerced solidly with activated platelets in monocyte-platelet complexes (MPC). MPC were selectively accrued in the blood of AAA. Pairwise analysis of blood and aortic tissue revealed increased accumulation of CD14 /CD14 + but not FCGR3A /CD16 + cells in AAA wall. In murine AAA modeled by angiotensin II infusion in ApoE -/- mice, we observed increased MPC in the circulation which correlated with increased inflammation in the aortic tissue. We further demonstrated that monocytes that bind to platelets are derived from the spleen. Splenectomy abrogated the formation of MPC and protected from AAA development in mice, similarly to targeted disruption of MPC. Here we show that interference with unbalanced circulating myeloid subsets and disruption of MPC are novel attractive avenues for therapeutic strategies in AAA.
Abstract 15756: The Beneficial Impact of Primary Care Providers’ Supply on the Cardiovascular Mortality Rates in the United States: A Nationwide Population Analysis 2011-2019
Authors: Shady Abohashem, Wesam Aldosoky, Ahmed Sayed, Taimur Abbasi, Tawseef Dar
Journal: Circulation (2022)

Introduction: United States is facing an increasing shortage of primary care physicians (PCP) and health care demands. However, data on the relationship between PCP availability and burden of cardiovascular mortality (CVM) and related disparities, is limited. Hypothesis: Herein, we evaluate the nationwide impact of county PCP levels on CVM in overall and within disparate populations stratified by age, sex, and race/ethnic subgroups. Methods: PCP is calculated as the ratio of PCPs to the population, using data from National Center for Health statistics. Age-adjusted CVM rates (ACVM) between 2011 to 2019, were obtained using CDC database. Behavioral Risk Factor Surveillance was utilized to acquire county characteristics and confounders. Poisson linear mixed model was employed. Results: Of 3143 U.S. counties, 2900 counties (62% white; 51% female; 14% aged ≥65) had data available on ACVM and PCP.In a multivariate model adjusted for demographics, CV risk, socioeconomic, and environmental factors, higher PCP levels significantly associated with lower ACVM (Standardized IRR: 0.979; 95% CI: 0.972 to 0.986), which translates to 4.8 fewer CV deaths each year (AYD). This effect was relatively higher in middle-aged [45-64] (IRR: 0.967) versus elderly [≥65] (IRR: 0.980), males (IRR: 0.981) versus females (IRR: 0.972), and within Whites (IRR: 0.976). Notably, the relative impact of PCP was greatest in [45-64] Whites (IRR: 0.963), while the absolute impact was highest amongst ≥65 males with 36 fewer CV deaths each year. ( Figure ). Conclusions: Higher PCP supply is robustly associated with lower ACVM, and that beneficial effect is most evident amongst both age and sex subgroups as well as non-Hispanic whites. Moreover, this association is significantly independent of potential confounders that have a plausible association with CVM. Therefore, population-level strategies to promote primary care access, are imperative for reducing the burden of CVM and promoting health equity.
Abstract 15249: Evidence for Clonal Proliferation of Smooth Muscle Cells in Unstable Human Atherosclerotic Lesions
Authors: Kenji Kawai, Atsushi Sakamoto, Michal Mokry, Saikat Ghosh, Weili Xu, Rika Kawakami, YU SATO, Masayuki Mori, Takao Konishi, Aimee Vozenilek, Renu Virmani, Gerard Pasterkamp, Aloke Finn
Journal: Circulation (2022)

Background: Studies using techniques that relied on expression of an X-linked gene suggested predominant clones of smooth muscle cells (SMC) may exist in human atherosclerosis. These studies were limited by spatial resolution and nature of plaque types studied. We investigated whether clones of SMCs exist in unstable human atheroma. Methods and Results: We used a 25 nucleotide deletion in the 3’ UTR of the BGN gene, highly expressed by SMC and prevalent in 30% of females, to study clonal proliferation. Three different types of plaques (erosion, rupture, and adaptive intimal thickening) were selected from females heterozygous for the deletion mutant. Hybridization of target RNA-specific BaseScope probes was conducted to visualize the distribution of mutants and images displayed as a bubble plots. Clonality index was calculated as the percentage of each probe in each ROI. A clonality index equal to or exceeding the three times the standard deviation above the mean of the clonality index of the media in all plaques was considered clonal. In comparing clonality between media and intima, the mean percent ROI with clonality was significantly higher in the intima than in the media (42.3±18.2 vs 18.3±9.6%, P=0.003) and this was consistent for both eroded (27.0±9.8 vs 9.0±3.8%, P=0.04) and ruptured plaques (41.3±10.7 vs 20.0±3.5%, P=0.03). The relationship of dominant clone in the intima and media shows significant concordance in the majority of plaques studied (R=0.72, P&lt;0.0001). Conclusions and Relevance: This novel approach suggests dominant clones exists within atherosclerotic lesions and may originate from the media.
Abstract 15303: Maternal Features for Live Births in Fontan Patients
Authors: Parvathy Ravi Sankar, Cassandra Garraud, Anna Scandinaro, Joshua M Saef, Joanna Ghobrial
Journal: Circulation (2022)

Introduction: As the population of women with congenital heart disease with prior Fontan palliation (PFPs) increases, doubling in size over the next 20 years, there will be a concordant need for multidisciplinary obstetrics care. There is an increased prevalence of miscarriage, maternal and fetal complications including arrhythmias, heart failure, premature birth, and neonatal death. We sought to review our single center experience in the context of an established cardio-obstetrics multidisciplinary team. Methods: Single-center retrospective cohort study of PFPs with live births who received care at our cardio-obstetrics clinic. A chart review was performed to identify maternal characteristics as well as fetal outcomes. Descriptive statistics were calculated using R Studio Statistical Software version 1.2.5033.Result: Ten women with PFPs and live births were identified. None had more than one live pregnancy. The average number of pregnancies was 2 (range 1-6). The mean gestational age was 31.2 weeks (range 23-37). Five patients were primigravida. Six of the pregnancies were planned and eight received preconception counseling. Baseline NYHA was 50% class I and 50% class II. The most common maternal comorbidity in patients with a live pregnancy was atrial arrhythmia, and the most common pre-pregnancy medication was warfarin. Prematurity, low birth weight, and associated comorbidities (see table 1) were common in this population. The average birthweight was 1,589g (range 460g-2210g). Indication for delivery was more commonly obstetric than maternal concern. No maternal strokes, thromboembolic events, cardiac arrests, maternal or infant deaths and rehospitalizations were noted. Conclusion: Maternal and fetal complications in mothers with PFP are common. A multidisciplinary approach in a specialized cardio-obstetrics clinic has the potential to improve outcomes. Larger cohort and long term outcomes are needed in this patient population.
Abstract 15520: The Relationships Between Daily Step Counts With All-Cause and Cardiovascular Mortality: A Meta-Analysis
Authors: Ibadete Bytyci, Stanislaw Surma, Joanna Lewek, Maciej Banach
Journal: Circulation (2022)

Introduction: There is good evidence that inactivity and walking less steps per day increase risk of cardiovascular (CV) disease and general health. However, the golden limit of steps and their role in health is still debatable. Hypothesis: The aim of this meta-analysis was to evaluate the relationship between step count and all-cause and CV mortality. Methods: We systematically searched all electronic databases from inception until 12 th June 2022. Main endpoints were all-cause mortality and CV mortality. Inverse-variance weighted random effects model was used to calculate the number of steps per day and mortality. Results: Eighteen cohort studies with a total of 67,111 (general healthy subjects and/or patients at cardiovascular risk) with a median follow up 6.9 years were included in the meta-analysis. A 1000-step increment was associated with 12% decreased risk of all-cause mortality HR 0.88 (95%CI: 0.85 to 0.91; p&lt;0.001), while a 500-step increment was associated with 6% decrease of CV mortality - HR 0.94 (95%CI 0.91 to 0.97; p&lt;0.001, Figure 1 ]. Compared to quartile with median steps per day 4038 used as reference quartile, the quartile 1 (Q1, median steps: 6201), quartile 2 (Q2, median steps 7094) and quartile 3 (Q3, median steps 11275) were associated with lower risk for all-cause mortality (49%, 55% and 67% respectively; p≤0.001 for all), and reduced cardiovascular mortality by 10 and 55% for Q1 and Q2, respectively (p≤0.02 for all ; Figure 2 ). Conclusions: This meta-analysis reveals the clear inverse association with the number of step count and all-cause and cardiovascular mortality with the largest health benefit for individuals with the highest number of steps daily.
Abstract 15468: Cd81 Interacts With Sodium Chloride Cotransporter in Lps-Induced Preeclampsia Rats and in Cultured Mouse Renal Distal Convoluted Tubule Cells
Authors: Xiaoyan Wang
Journal: Circulation (2022)

Kidney regulates blood pressure mainly through salt/water reabsorption affected by sodium transport proteins along nephron. We have reported that placental CD81 plays an important role in the pathogenesis of preelampsia. In order to explore the connection between CD81 and renal sodium transport proteins in preelampsia, we studied their interactions in vivo and in vitro. On the gestation day 18 of lipopolysaccharide-induced preeclamsia model rats with hypertension and albuminuria, the renal protein abundances of NKCC2 (150±14,% of control, n=5-6/group, mean±SE, t-test, same as below), p-NKCC2(567±70%), NCC (254±41) and WNK4 (196±12) were increased together with an increase of CD81 in kidney (225±46) and urinary exosomes(396±100). Renal NCC (215±30) was elevated while NKCC2 tended to increase at 17000g pellet in LPS group. There was no change of both NKCC2 and NCC at 200,000g pellet. In kidney homogenates, CD81 was coimmunoprecipitated with NKCC2, NCC, not NHE3 while NKCC2, NCC were coimmunoprecipitated with CD81 not CD63. In renal plasma-membrane-enriched fraction NCC, not NKCC2, was also increased in preeclampsia rats. In the apical membrane of renal tubules CD81 was colocalized with NCC while minimum colocalization was found between CD81 and NKCC2. In cultured mouse distal convoluted tubule cells, CD81 was colocalized with NCC while CD81 deletion with siRNA decreased NCC and partially reversed lipopolysaccharide-induced increase of NCC. Furthermore, CD81 was detected only in the urinary exosomes from preeclampsia patients along with increases in NKCC2 (6063±811) and NCC(1085±191)relative to normal pregnant women (n=6/group, t-test). Those findings suggest that CD81 interacts with renal NCC in vivo and in vitro and the increase of renal CD81 may up-regulate NCC, possibly NKCC2 as well, and contribute to the increased blood pressure in preeclampsia.
Abstract 15840: Comparison of Risk Factors for Single, Double, and Multivessel Coronary Artery Disease in a Cohort Undergoing Coronary Revascularization
Authors: Muhammad Asim Shabbir, Moiz Ehtesham, Waseem Amjad
Journal: Circulation (2022)

Introduction: Hypertension (HTN), dyslipidemia (HLD), smoking, obesity, and diabetes (DM), peripheral arterial disease (PAD) are known risk factors for coronary artery disease (CAD). However, it is not clear if one risk factor is related to causing higher plaque burden than others. We attempted to find relationship of these risk factors with number of occluded coronary arteries (&gt;50% stenosis) to assess plaque burden. Methods: Retrospective analysis of patients admitted to a tertiary care center undergoing coronary revascularization (PCI or CABG) for acute myocardial infarction (AMI) from May 2019 - May 2021. Patients were classified based on the number of occluded coronary vessels: single vessel disease (SVD), 2 vessel disease (2VD), and &gt;2 or multivessel disease (MVD). CAD risk factors were analyzed. CAD burden was assessed by number of vessels showing &gt;70% stenosis angiographically. The relationship between CAD risk factors and CAD burden was analyzed via univariate and multivariate analysis. Results: A total of 434 patients were included. Mean age was 56 ± 11 years with 61% Caucasians, 33% African Americans (AA), and 6% Hispanics. Females were 39.4%. Patients with SVD, 2VD, and MVD, were 264 (60.8%), 101 (23.3%) and 69 (16%) respectively. Smoking and diabetes were more prevalent in SVD group, while AA race was associated with higher incidence of MVD (table 1). HTN, HLD, diabetes, obesity, smoking, PAD, CKD were statistically similar with respect to CAD burden. On multivariate analysis, AAs {OR 0.13 [0.07-0.23]} and Hispanics {OR 0.22 [0.09-0.54]} had a lower prevalence of SVD compared to Caucasians. AA had higher odds of MVD {6.2 [2.9-12.9]} shown in table 2. Mortality was higher in MVD group compared to SVD (24.6% vs. 40.6%, p=0.01). Conclusions: African American patients had a higher CAD burden when presenting with AMI. HTN, HLD, diabetes, obesity, PAD, smoking and CKD were statistically similar when compared for CAD burden.
Abstract 15646: The Need for Speed - Early Experience of Very High-Power Short Duration (QDOT <sup>TM</sup> ) Ablation
Authors: Ronan Walsh, Fiona Kehoe, Stephen Frohlich, Noelle Murphy, Derek Crinion, Jonathan C Lyne
Journal: Circulation (2022)

Introduction: Ablation is a cornerstone of therapy for atrial fibrillation (AF), as well as one of the most common procedures in electrophysiology. Use of intermediate-power ablation has given way to high-power short duration radiofrequency ablation. However, more recently the emergence of very high-power very short duration (vHPvSD) ablation at 90W may prove to be more efficient and effective in the management of AF. The radius of the resistive heating zone is increased, while the conductive heating zone tapers off more quickly, potentially reducing collateral tissue damage. Methods: This was a single centre prospective study using the QDOT TM (Biosense Webster, Irvine, California) ablation catheter. Our workflow involves double trans-septal puncture via TOE guidance, use of a deflectable sheath, LASSO 10-pole mapping for first time AF ablations or PENTARAY TM for redo procedures, ablation while paced in sinus rhythm were possible, general anaesthetic, low tidal volumes, and an I:E ratio of 1:4. All pulmonary vein isolations (PVI) and posterior wall isolations (PWI) were performed at 90W for 4s, while cavo-tricuspid isthmus (CTI) lines were completed using QMode at 40W for 20s. Results: 65 patients under went vHPvSD for treatment of atrial fibrillation. Of these 12 were re-do cases that had previously been treated with either radiofrequency or cryo-ablation. The average age was 58.9±9.7 (yrs) with 73% males. Paroxysmal atrial fibrillation was seen in 69%, 31% had persistent AF, and 7% had co-morbid atrial flutter. The average CHADSVASC score was 1.18±1.03. Pulmonary vein isolation was achieved in 100% of patients, 10% had posterior wall isolation, and 16% underwent cavo-tricuspid isthmus ablation. Average skin-to-skin and total ablation times were 58.2±13.1 (mins) and 23.4±6.5 (mins), respectively. Average RF time was 8.1±0.7 (mins). Mean follow up was 126±21 days, where 2 recurrences were seen. We saw no complications in our patient cohort. Conclusions: The method of vHPvSD is safe and durable in the treatment of atrial fibrillation. Total procedure time and RF time were significantly lower than previous RF ablation therapies. This relatively large study on the safety and early efficacy of vHPvSD adds to the emerging data on this promising technology.